Disrupted Insulin Signaling Causes Pain Hypersensitivity In Diabetes

Recent study suggests that impaired insulin signaling in pain
sensing neurons may be causing diabetes associated pain, contrary to
currently held views.

A frequent complication of diabetes
is chronic pain, increased pain sensitivity, numbness and tingling;
treatment options are limited and often ineffective.

Findings of the latest study may
pave the way for development of newer and better treatments for diabetic
pain and neuropathy.

Improper
insulin signaling in pain sensory nerve fibers may be responsible for the
chronic pain associated with diabetes according to new research led by Dr Seol
Hee Im and Dr Michael Galko from the University of Texas MD Anderson Cancer
Center.

Disrupted Insulin Signaling Causes Pain Hypersensitivity In Diabetes

The
currently held theory states that pain associated with is a secondary effect of
micro-vessel
(vascular) changes and toxicity of high blood sugar levels to nerve damage.
However, latest research using a fruit fly model suggests that disrupted
insulin signaling
in pain sensory neurons may be actually responsible. The findings of the study
are published in the open access journal Disease Models &
Mechanisms.

Reason for Study

The mechanisms of diabetes-induced
pain remain still largely unclear.
Till date, most studies have used
vertebrate animal models such as mice to determine how increased sugar
levels might be affecting blood vessels and nerves.

However, a wider investigation into whether other factors and tissues could be
involved in the development of disease-associated pain symptoms has not been undertaken
still.

The
team hope to address this gap and
determine whether other mechanisms could be at play in this disabling condition
and gain insight into the pathogenesis of diabetic pain through the use of the fruit fly
model.

Details of Study

The
fruit fly model for diabetic pain study described in this research publication
is not new but an extension of well-established fruit fly models used in
previous diabetes research, as well as assays for measuring pain in fly larvae.

‘Agents that modify insulin signaling may result in better and more effective treatments for diabetic pain.’

The
crucial questions that the study team hoped to answer were

whether the pain hypersensitivity in
persons with diabetes is related to defects in insulin signaling in
sensory neurons

whether this pain can be modeled in
fruit flies

To
answer these critical questions, the team employed three types of fruit fly models with different attributes namely

two
more fruit fly models with established type 1 and type 2 diabetes respectively

Key Findings of Study

In the fruit fly model with
disrupted insulin signaling, the team found to their surprise that the
insulin receptor protein showed activity in pain sensory neurons instead
of functioning in metabolic tissues such as muscle and fat.

The faulty insulin
receptor function in these flies caused persistent hyper-activation
of the neurons and pain hypersensitivity.

In both the genetic knock-down,
as well as type 2 diabetes model flies, the scientists were able to reverse pain hypersensitivity by
increasing insulin signaling in the pain sensory neurons.

Thus
the findings of the study suggest that impaired insulin signaling may be
responsible for pain hypersensitivity in diabetic patients and reversing it may
reduce or prevent the pain.

The
leaders of the study team, Dr Seol Hee Im and Dr Michael Galko from the University
of Texas MD Anderson Cancer Center, explain that, "Only very recently have
researchers started to pay attention to
the loss of insulin signaling in the pain sensory neurons. This is a gap
that our work has helped to fill in - the Drosophila model has allowed
tissue-specific manipulation of insulin signaling and measurement of the
ensuing effects on pain sensitivity."

About Fruit Flies

Fruit
flies or Drosophila melanogaster are not new to research and have been used in
genetic and developmental biological research for ages. Additionally, they have
been used as a model organism for several aspects of diabetes research,
including studies into the molecular mechanisms of maintaining optimal glucose
levels, insulin production and sensitivity. They have also been used to study
other diabetes-associated complications such as metabolic syndromes and obesity
induced heart disease.

Diabetic Pain

The
condition predominantly affects the lower legs and feet. Symptoms may vary from
mild to painful, debilitating and even fatal. Symptoms include pain and
tingling and numbness in the feet and legs. Treatment includes managing blood
sugar levels and using drugs to control symptoms.

Future Research Plans

The team plans to use the type 2
diabetes fly model to determine specifically which genes are necessary to
maintain persistent hypersensitivity in pain sensory neurons for possible
targeting in future.

Drs
Im and Galko say, "Such screens can be either genetic or chemical in
nature and could be performed in our models of genetic mutants or
tissue-specific Insulin receptor knockouts as well. We can also expand our
analysis to other sensory modalities such as cold or mechanical and chemical
stimuli, as diabetes patients also experience these hypersensitivities."

The role of insulin signaling in
diabetic neuropathy and diabetic pain could
be extended into vertebrate models to learn if the role of insulin
signaling in pain fibers is preserved across species.

Patients with diabetes are prone to suffer from complications in most parts of the body. Diabetes can affect all types of nerves, the sensory, motor as well as the autonomic. Test your knowledge on diabetic neuropathy by taking this ...

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